Mutation of Genes and Psoriasis

 

Genetic Mutation and Psoriasis

      PKGhatak,MD

Every function of the cell, from the time of conception to the very end of life, is guided by the instructions inscribed in the genes. These functions can be grouped as Innate, adaptive and aberrant.

The skin is a large and special organ. It is entirely exposed to the elements of the outer world (except the parts we intentionally keep covered by clothing). The surface layers of the skin must be replaced at a constant and consistent rate as they are lost and that is the Innate function; some of the cell functions have to be modified according to the changes in the external environment and changes in the body from infections, other diseases or nutritional causes and these are adaptive function. The aberrant functions are due to the mutation of genes and Psoriasis is one of them.

In psoriasis, the cells of the surface layer of the skin grow at a rapid rate and the new cells accumulate over the older cells before the old cells have time to fall off. The accumulated patches are called Plaques. Inflammatory cells infiltrate the skin and underneath the plaques, the blood vessels multiply in numbers causing an increase in the blood supply producing itching. The top layer of dead cells of the plaques appears as pale white to silvery flakes and dandruff on the scalp and is shed off easily. These plaques may be present over the elbows, knees, lower back, scalp and face. It may appear as pink or red scaly drop like lesions in children and is known as Guttate psoriasis. Plaques underneath the breasts, buttocks, and groins are called Flexural psoriasis. In some cases, the entire skin is covered with dead loose cells and the color of the skin turns red from the increase in blood supply and this is called Erythrodermic psoriasis. Lesions on palms and soles of feet appear as pustules called Pustular psoriasis. Psoriasis also affects nails and joints and is called psoriatic arthritis.

Study methods.

Study of families of multiple members affected by psoriasis, studies of affected twins, and analysis of whole genome for the presence of mutations of genes in psoriasis patients, methylation of genes which modify gene functions without altering DNA sequence are commonly employed methodologies to investigate the role of hereditary and or phenotype mutation of genes in psoriasis.

The mutation of gene/genes in T-lymphocytes and B-lymphocytes leads to altered functions of Interleukins and Cytokines. These interrelated changes ultimately alter the rate of cell divisions and programmed cell deaths, inflammatory responses and generate autoimmune diseases.

Over 80 mutated genes are associated with psoriasis. However, the genetic mutation in psoriasis in not more than 20 % of all cases of psoriasis. The cause of the rest is unknown. Investigators advanced various theories from poison to pollution of the environment but definitive evidence is lacking.

Reports from Saudi Arabia indicate 5 % of the adult population suffers from psoriasis. The prevalence of adult psoriasis in China is 0.5 %, in Norway-11 %, in USA -3 %, black to white- 3 to 1 ratio, in India -2%, in Western Europe -3 %, and in Latin America 2%.                 

Known gene mutation.

Mutated genes associated with psoriasis are called PSORS and are designated 1 through 9 numerically. These genes are present on Chromosomes 1 to 22, of which frequent mutation was seen in chromosomes nos.1.6,9,17 and 19. These mutations may be at one locus or in multiple loci. In the Chinese population mutation of genes on chromosome 1 is most frequent, in Europe, the mutation is frequent on chromosome 17. Studies in Saudi Arabia show autosomal dominant inheritance with mutation of a gene on chromosome 17 q25 (on the long arm of chromosome at band location 25) and q4 loci.

Human leukocyte antigens (HLA) B-13, B-17, B-57, and CW6 are associated with psoriasis. About 70 % of HLA mutation is due to HLA CW6.

Interleukin-36 amplifies TH-17 lymphocytes.

Gene-wide association (GWA) identified 16 loci. CD4 helper T cells and CD8 cytotoxic T cells are associated with psoriasis.

Genetic mutations alone may not by themselves be the cause of psoriasis but in association with additional factors are responsible for psoriasis. Publications from WHO indicate infections, poisonous agents in the air and water, stress, obesity, cigarette smoking, and concurrent autoimmune diseases- special Crohn's disease are triggering factors. All these factors, namely genetic predisposition, and hereditary and triggering factors lead to internal changes in the body and lead to the development of the chronic inflammatory autoimmune disease - psoriasis.

 

**********************************************************